The HLA class I molecules are crucial in the recognition by cytolytic T lymphocytes (CTL) of their targets. In virus infected cells, fragments of viral peptides bind to class I molecules and this class I/peptide complex is recognized by CTLs. T cells are important in the clearance of nearly all virus infections. In the experiments proposed here we will examine the binding of HIV encoded peptides to MHC class I molecules, and the relationship between binding and CTL recognition. In addition, we will undertake a detailed analysis of the interaction between HIV peptides and class I products using a combination of peptide synthesis, and saturation mutagenesis of the HLA genes. These experiments will provide important information on the binding of HIV peptides of HLA and lay the groundwork for the development of synthetic vaccines which can take into account the variability of HLA.